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Publications

Journal Article Ppublish

PubMed: 42307017 DOI: 10.1002/eji.70223

Spatial and Phenotypic Heterogeneity of ILC Subsets in Mouse Lung Under Type 2 Inflammatory Conditions.

Eur J Immunol 56(6):e70223

Authors: Sandy Kroh, Anna Pascual-Reguant, Artür Manukyan, Ralf Uecker, Robert Günther, Lars Philipsen, Ralf Koehler, Peggy Mex, Markus Landthaler, Raluca A Niesner, Anja E Hauser

Affiliations

  • Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Immune Dynamics, Deutsches Rheuma-Forschungszentrum (DRFZ), a Leibniz Institute, Berlin, Germany.
  • Centre Nacional d'Anàlisi Genòmica (CNAG), Barcelona, Spain.
  • Universitat de Barcelona, Barcelona, Spain.
  • Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine, Berlin, Germany.
  • Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke-University, Magdeburg, Germany.
  • Multi-parametric bioimaging and cytometry (MPBIC) core facility, University Hospital, Otto-von-Guericke-University, Magdeburg, Germany.
  • Institute of Cellular and Molecular Immunology, University Hospital, Otto-von-Guericke-University, Magdeburg, Germany.
  • Immune Dynamics, Deutsches Rheuma-Forschungszentrum (DRFZ), a Leibniz Institute, Berlin, Germany. EMBL Node in Single Molecule Science, Department of Molecular Medicine, School of Biomedical Sciences, Faculty of Medicine & Health, University of New South Wales, Sydney, Australia.
  • Veterinary Medicine, Dynamic and functional in vivo Imaging, Freie Universität Berlin, Berlin, Germany. Biophysical Analytics, Deutsches Rheuma-Forschungszentrum (DRFZ), a Leibniz Institute, Berlin, Germany.
  • Institut für Biologie, Humboldt-Universität zu Berlin, Berlin, Germany.
  • Veterinary Medicine, Dynamic and functional in vivo Imaging, Freie Universität Berlin, Berlin, Germany.
  • Biophysical Analytics, Deutsches Rheuma-Forschungszentrum (DRFZ), a Leibniz Institute, Berlin, Germany.

Abstract

As key regulators of mucosal immunity, innate lymphoid cells (ILCs) are involved in tissue homeostasis, inflammation, and repair. Studying ILCs within their native microenvironment remains challenging due to the low abundance of these tissue-resident immune cells. Here, we applied cyclic multiplex immunofluorescence, namely multiepitope ligand cartography (MELC), in a systemic IL-33-induced type 2 inflammation model to spatio-temporally characterize ILC phenotype and localization in mouse lungs. Niche analysis with all identified cell types resulted in four distinct niches and an expansion of a mixed B and Plasma cell (BPC)/blood endothelial cell (BEC) niche, while the niche predominated by blood endothelial cells decreased at IL-33 day 3. Spatial neighborhood and coenrichment analyses revealed ILC2 accumulation in myeloid-rich peri-lymphatic niches at early time points of IL-33-mediated inflammation. ILC2s were in direct contact with activated alveolar macrophages and lymphatics. While they expressed ICOS under homeostatic conditions, pronounced expression of MHCII at days 1 and 3 of IL-33 stimulation was observed. Unlike ILC2s, NK cells/ILC1s were coenriched near blood vessels, next to B cells and plasma cells. Our findings demonstrate the utility of spatial multiplex imaging for dissecting rare immune cell localization and phenotypes and uncover dynamic, tissue-specific remodeling of ILC niches during early type 2 inflammation.

MeSH

Cells, Lung, Blood, Plasma Cells, Phenotype, Proteomics, Endothelial Cells, Tissues